This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This research will focus on the effect of salt on blood pressure (BP) and downstream targets of the renin-angiotensin-aldosterone system (RAAS) as well as markers of oxidative stress as potential mechanisms underlying impaired nitric oxide (NO)-mediated endothelial function. We hypothesized that in genetically- susceptible non-hypertensive AA, high salt induces oxidative stress (via local vascular activation of RAAS) that impairs NO-mediated endothelial function to a greater extent in salt sensitive (SS) than in salt-resistant (SR) counterparts. It is anticipated that angiotensin-converting enzyme inhibition may represent a target for early intervention to ameliorate the alterations in vascular blood flow. Other examinations will assess the state of vascular function at baseline and after manipulations of angiotensin levels. As BP alone only partially accounts for end-organ responses to salt, genetic susceptibility to salt-sensitivity will be also examined. Specific Aims: 1) define potential mechanisms of alterations in vascular function in response to acute changes in Na balance in non-hypertensive AA and 2) compare the vascular end-organ responses to salt/volume challenges with polymorphic variants of selected candidate genes related to RAAS and Na transport. This carefully designed physiological study will combine manipulations of salt and angiotensin levels with novel markers of oxidative stress to probe vascular/cardiorenal function in this unique population of non-hypertensive AA subjects at risk for end-organ dysfunction.